The present proposal is a resubmission of 1R01 MH59784-01, "Treatment of Negative Symptoms and Cognitive Impairments," a four site multicenter application designed to assess the efficacy of the glutamatergic agents, d-cycloserine and glycine, for the treatment of persistent negative symptoms and cognitive impairments in patients with schizophrenia. These manifestations of schizophrenia account for much of the long-term morbidity, impaired social and occupational functioning, and poor quality of life observed in patients with schizophrenia. Persistent negative symptoms may either be primary (deficit symptoms) or secondary. At present, conventional and novel antipsychotics have limited efficacy for secondary negative symptoms, and there are no known effective treatments for these deficit symptoms. There are also no known agents with robust efficacy for cognitive impairments. The long-term objective of this application is to develop an effective treatment for persistent negative symptoms, both primary and secondary, and cognitive impairments. The Specific Aims are to examine whether: 1) d-cycloserine and/or glycine is superior to placebo for the treatment of persistent primary and secondary negative symptoms; and 2) d-cycloserine and/or glycine is superior to placebo in the treatment of cognitive impairments in deficit and nondeficit patients. Secondary goals include: a) to establish a standard clinical trial methodology to assess the therapeutic efficacy of potential treatments of persistent negative symptoms and cognitive impairments; and b) to describe the relationship between cognitive impairments, as assessed by neuropsychological test performance, and negative symptoms in the clinical trial context. The study will be a 16-week double-blind, parallel groups comparison of adjunctive medication (i.e., d-cycloserine and glycine) to placebo. Neuropsychological tests will be used to assess cognitive functioning, and will be administered at baseline and at the end of the study. The study will provide new information on the efficacy of d-cycloserine and glycine for both persistent primary and secondary negative symptoms and theirs effects on cognitive functioning.